1. Field of the Invention
The most widely used antibiotics are undoubtedly those pertaining to the class of beta-lactams. It has been known for many years that when these antibiotics are used in clinical therapy their “in vivo” effectiveness progressively diminishes because of beta-lactamase enzymes capable of degrading the beta-lactam ring. Fortunately, the discovery of certain substances able to inhibit the activity of the aforesaid enzymes has enabled certain beta-lactam antibiotics, ineffective if used alone, to be still used by bringing them into association with the said inhibitors. These antibiotics include piperacillin, which is administered by injection as the sodium salt. Following the decay of its therapeutic effectiveness for the aforesaid reason, piperacillin was associated with tazobactam sodium.
2. Discussion of the Related Art
Piperacillin sodium is normally prepared by lyophilization, the very soft lyophilizate obtained ensuring rapid solubilization, as described in U.S. Pat. No. 4,477,452 and U.S. Pat. No. 4,534,977. It is therefore evident that the lyophilization of piperacillin or of an association in which it is present in a prevalent percentage is little productive, precisely because the operation has to be carried out in very dilute solution. On the other hand, mixing piperacillin sodium with separately lyophilized tazobactam sodium presents a problem caused by the different densities of the two components: in this respect, in the mixture a non-homogeneous distribution of the powders occurs in the sense that the tazobactam sodium, of greater density than piperacillin sodium, tends to separate within the lower layers of the mixture.
U.S. Pat. No. 5,763,603 claims a crystalline sodium salt of tazobactam, but even using this crystalline salt the problem of homogeneity of the mechanical mixture of the piperacillin and tazobactam sodium salts can evidently not be solved because of the low density of lyophilized piperacillin sodium.
This fact evidently means that piperacillin sodium and tazobactam sodium mixtures cannot be prepared in quantities greater than those of a single injectable dose.